Sensitivity analysis for m-estimates, tests, and confidence intervals in matched observational studies

Huber's m-estimates use an estimating equation in which observations are permitted a controlled level of influence. The family of m-estimates includes least squares and maximum likelihood, but typical applications give extreme observations limited weight. Maritz proposed methods of exact and approximate permutation inference for m-tests, confidence intervals, and estimators, which can be derived from random assignment of paired subjects to treatment or control. In contrast, in observational studies, where treatments are not randomly assigned, subjects matched for observed covariates may differ in terms of unobserved covariates, so differing outcomes may not be treatment effects. In observational studies, a method of sensitivity analysis is developed for m-tests, m-intervals, and m-estimates: it shows the extent to which inferences would be altered by biases of various magnitudes due to nonrandom treatment assignment. The method is developed for both matched pairs, with one treated subject matched to one control, and for matched sets, with one treated subject matched to one or more controls. The method is illustrated using two studies: (i) a paired study of damage to DNA from exposure to chromium and nickel and (ii) a study with one or two matched controls comparing side effects of two drug regimes to treat tuberculosis. The approach yields sensitivity analyses for: (i) m-tests with Huber's weight function and other robust weight functions, (ii) the permutational t-test which uses the observations directly, and (iii) various other procedures such as the sign test, Noether's test, and the permutation distribution of the efficient score test for a location family of distributions. Permutation inference with covariance adjustment is briefly discussed.     

Brucellacapt、RBT、SAT、iELISA四种血清学检测方法对布鲁氏菌病检测价值的比较研究

目的:探讨布鲁氏菌病血清学试验(Brucellacapt)、虎红平板凝集试验(RBT)、试管凝集试验(SAT)、间接酶联免疫吸附试验(i ELISA)四种血清学检测方法对布鲁氏菌病检测价值的比较研究。方法:收集近两年110例布鲁氏菌病疑似病例人员的静脉血分离得到血清后进行Brucellacapt、RBT、SAT、i ELISA四种血清学检测,以卫生部制定的《布鲁氏菌病诊疗指南》中布鲁氏菌病确诊方法为诊断金标准,将检测结果与其确诊结果进行比较,评价比较各组血清检测方法对布鲁氏菌病的检测价值。结果:110例疑似人员中确诊为布鲁氏菌病阳性91例、阴性19例。Brucellacapt试验阳性89例、阴性21例;RBT试验阳性79例、阴性31例;SAT试验阳性71例、阴性39例;i ELISA检验阳性82例、阴性28例。Brucellacapt试验的灵敏度、符合率、Kappa值、ROC曲线下面积均最大,i ELISA试验、RBT试验、SAT试验依次减小;i ELISA试验的ROC曲线下面积最大,Brucellacapt试验次之,其次为RBT试验,SAT试验的ROC曲线下面积最小。结论:Brucellacapt、RBT、SAT、i ELISA四种血清学检测方法对于布鲁氏菌病检测均有一定的检测价值,对于常规普通患者可采用RBT试验、SAT试验进行检查,而对于疑似病例人员可采用灵敏度更高的Brucellacapt试验、i ELISA试验。     

Properties and Application of the Location-Test V (n,k)

The present paper is concerned with the properties of a test statistic V(n, k) to test location differences in the one-sample case with known hypothetical distribution G(x). The test is similar to the WILCOXON two-sample statistic after replacement of the second sample by quantiles of the hypothetical distribution. A comparison with the exact distribution of V(n, k) shows that an approximation by means of the normal distribution provides good results even for small sample sizes. The V-test is unbiased against one-tailed alternatives and it is consistent with a restriction which is hardly relevant in practical applications. With regard to the application we are interested especially in the power and robustness against extreme observations for small sample size n. It is shown that in a normal distribution with known standard deviation V(n, k) is more powerful than STUDENT's t for small n and more robust in the sense considered here. The test statistic is based on grouping of the observations into classes of equal expected frequency. A generalization to arbitrary classes provides an essential extension of applicability such as to discrete distributions and to situations where only relative frequencies of G(x) in fixed classes are known.     

广东深圳湾和海南新村港底质中的有孔虫

广东深圳湾和海南新村港均为非正常海相的潟湖型港湾,有孔虫十分贫乏,分异度很低,经初步坚定,计18属34种,其中包括3新种及3未定种。深圳湾以胶结壳有孔虫占优势,几乎不见瓷状壳,称Haplophragmoides shenzhenensis sp.nov.-Ammonia of.beccarii(Linne)组合;新村港则以瓷状壳占优势,未见胶结型壳,建立Triloculina trigonula(Lamaark)-Peneroplis planatus(Fichtel et Moll)组合。对两地各种不同类型的有孔虫壳体作成分分析及酸溶试验,表明水体的pH值是有孔虫分布差异的控制因子。     

Differential role of the hippocampus, amygdala, and dorsal raphe nucleus in regulating feeding, memory, and anxiety-like behavioral responses to ghrelin

Ghrelin is a peptide hormone produced and secreted from the stomach. Hypothalamic injection of the peptide increases food intake but it is not known if the peptide affects other brain regions. We measured several behavioral parameters such as anxiety (elevated plus maze), memory retention (step down test), and food intake after injections of different doses of the peptide in the hippocampus, amygdala, and dorsal raphe nucleus (DRN). The injection of ghrelin in the hippocampus and DRN significantly and dose dependently increased food intake in relation to controls rats, while injections into the amygdala did not affect the food intake. We also show for the first time that ghrelin clearly and dose dependently increases memory retention in the hippocampus, amygdala, and DRN. Moreover, ghrelin at different potencies induced anxiogenesis in these brain structures while the highest dose of 3 nmol/microl was effective in all of them. The comparison of sensitivity of each brain structure indicates a specific role of them for each of the behaviors studied. The results provide new insight in to the anatomical substrate and the functional role of extrahypothalamic ghrelin targets in the CNS.     

Nodakenin, a coumarin compound, ameliorates scopolamine-induced memory disruption in mice

Nodakenin is a coumarin compound initially isolated from the roots of Angelica gigas. In the present study, we investigated the effects of nodakenin on learning and memory impairments induced by scopolamine (1 mg/kg, i.p.) using the passive avoidance test, the Y-maze test, and the Morris water maze test in mice. Nodakenin (10 mg/kg, p.o.) administration significantly reversed scopolamine-induced cognitive impairments in the passive avoidance test and the Y-maze test (P<0.05), and also reduced escape latency during training in the Morris water maze test (P<0.05). Moreover, swimming times and distances within the target zone of the Morris water maze were greater in the nodakenin-treated group than in the scopolamine-treated group (P<0.05). In an in vitro study, nodakenin was found to inhibit acetylcholinesterase activity in a dose-dependent manner (IC(50)=84.7 microM). In addition, nodakenin was also found to inhibit acetylcholinesterase activity for 6 h in an ex-vivo study. These results suggest that nodakenin may be a useful for the treatment of cognitive impairment, and that its beneficial effects are mediated, in part, via the enhancement of cholinergic signaling.     

Exact,Distribution Free Confidence Intervals for Late Effects in Censored Matched Pairs

When comparing censored survival times for matched treated and control subjects, a late effect on survival is one that does not begin to appear until some time has passed. In a study of provider specialty in the treatment of ovarian cancer, a late divergence in the Kaplan–Meier survival curves hinted at superior survival among patients of gynecological oncologists, who employ chemotherapy less intensively, when compared to patients of medical oncologists, who employ chemotherapy more intensively; we ask whether this late divergence should be taken seriously. Specifically, we develop exact, permutation tests, and exact confidence intervals formed by inverting the tests, for late effects in matched pairs subject to random but heterogeneous censoring. Unlike other exact confidence intervals with censored data, the proposed intervals do not require knowledge of censoring times for patients who die. Exact distributions are consequences of two results about signs, signed ranks, and their conditional independence properties. One test, the late effects sign test, has the binomial distribution; the other, the late effects signed rank test, uses nonstandard ranks but nonetheless has the same exact distribution as Wilcoxon's signed rank test. A simulation shows that the late effects signed rank test has substantially more power to detect late effects than do conventional tests. The confidence statement provides information about both the timing and magnitude of late effects (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Tunic cells in pyrosomes (Thaliacea, Urochordata): cell morphology, distribution, and motility

Abstract. Cellular components of the tunic were histologically examined in 3 pyrosome species representing all 3 genera of the order: Pyrosoma atlanticum, Pyrosomella verticillata , and Pyrostremma spinosum . Three cell types are distributed in the tunic. Tunic amebocytes, irregularly shaped and motile, often contain granules and/or phagosomes. Spherical tunic cells contain many round vesicles with eosinophilic and acidic materials. Tunic net cells form a cellular network in which their long filopodia connect with one another. The net cells are densely distributed just beneath the tunic surface lining the common cloacal cavity and may produce tension to maintain the colony shape. The presence of net cells suggests a phylogenetic relationship between pyrosomes and some aplousobranch ascidians. Test fibers are multicellular cords that run in the tunic and connect the zooids. In P. atlanticum , they are attached to they are attached to the epidermal cells of the zooids, and transverse cloacal muscles are attached to the other (proximal) side of the epidermal cells. The test fibers may mediate coordination of the zooids and control muscle contraction.     

Effects of curcumin on the social behavior,blood composition,reproductive hormones in plasma and brain acetylcholinesterase in cadmium intoxicated mice

Cadmium (Cd) exposure can induce acute lethal health-related threats in humans since it has an exceptional ability to accumulate in living organism tissues and cause toxicological effects. Curcumin (Cur) on the other hand has a wide variety of biological activities and several studies have suggested its potential therapeutic or protective effects against several ailments and infections.To study the effect of Cur on the toxicity of Cd, Swiss–Webster strain male and female mice (sixty each) were divided into 6 groups of ten each at random. Group-1 served as the naïve control and received no treatment. Group-2, 3 and 4 were the experimental controls and were administered once a day with a single oral dose of 50% dimethyl sulfoxide (DMSO), Cur (300 mg/kg) or Cd (100 mg/kg) respectively, for 2 weeks. Group-5 and 6 received Cur and Cd in combination once a day orally for 2 weeks except that Cur in a dose of 150 and 300 mg/kg to group 5 and 6 respectively, was administered one hour before Cd administration to both groups.After treatment period, the male animals were subjected to social standard opponent test and females were subjected to the tube restraint tests and thereafter, their blood was collected to measure the blood composition indices and level of reproductive hormones. The animals were sacrificed to collect their brain for the estimation of acetylcholinesterase (AChE).Results indicated that Cd significantly increased nonsocial activities in males and latency to first bite in females, whereas the social activities in males and the number of bites in females were significantly decreased. All measured indices of blood composition and levels of progesterone (female) and testosterone (male) in blood and AChE in their brain tissues were significantly decreased due to Cd treatment.However, administration of Cur along with Cd had an ameliorating effect on all the behavioral and biochemical parameters studied herein and reduced the toxicity of Cd significantly and dose-dependently. Thus, Cur may be beneficial for general health and for protection from Cd intoxication.     

A Unifying,Analytic Model for Certain Linear Rank Tests. Part II: Exact Distribution Algorithms

On the basic of the analytic properties of the unifying model developed in the earlier Part I of this presentation, exact distribution algorithms are developed for the Wilcoxon 2-sample sum-of-rank test, the Freund-Ansari scale test, and the Wilcoxon signed-rank test. For the signed-rank test, provisions are made for zero-differences.     

旅游干扰对历山亚高山草甸优势种群种间相关性的影响

基于2×2列联表,应用方差比率法、χ2检验、Pearson相关系数检验及Spearm an秩相关系数检验等数量分析方法研究了旅游干扰对山西历山舜王坪亚高山草甸种间关联程度的影响。结果表明:(1)不同旅游距离带的联结指数(VR)均大于1,但统计量W均界于χ2分布的上下临界值之间。群落总体呈正关联,但联结性较弱,种的分布相对独立。(2)随着距游径距离的增加,4条不同旅游距离带的联结指数(VR)呈下降趋势;正负关联比有所增加,2χ检验显著率、Pearson相关检验显著率和Spearm an秩相关检验显著率都明显下降,说明旅游干扰对舜王坪亚高山草甸种间关联程度产生了一定的影响,距离游径越远,种间关联越趋于随机性,但这种影响尚未引起种间联结性的改变。(3)χ2检验与Pearson相关系数检验、Spearm an秩相关系数检验结果用来刻划种间相关性具有一定的相似之处,但仍存在一定差异,结合使用效果更好。与Pearson相关检验相比,Spearm an秩相关检验更具灵敏性。4)本研究结果支持随着群落演替进程的发展,群落种群总体向着无关联发展的观点。     

Adaptive seamless clinical trials using early outcomes for treatment or subgroup selection: Methods,simulation model and their implementation in R

Adaptive seamless designs combine confirmatory testing, a domain of phase III trials, with features such as treatment or subgroup selection, typically associated with phase II trials. They promise to increase the efficiency of development programmes of new drugs, for example, in terms of sample size and/or development time. It is well acknowledged that adaptive designs are more involved from a logistical perspective and require more upfront planning, often in the form of extensive simulation studies, than conventional approaches. Here, we present a framework for adaptive treatment and subgroup selection using the same notation, which links the somewhat disparate literature on treatment selection on one side and on subgroup selection on the other. Furthermore, we introduce a flexible and efficient simulation model that serves both designs. As primary endpoints often take a long time to observe, interim analyses are frequently informed by early outcomes. Therefore, all methods presented accommodate interim analyses informed by either the primary outcome or an early outcome. The R package asd , previously developed to simulate designs with treatment selection, was extended to include subgroup selection (so-called adaptive enrichment designs). Here, we describe the functionality of the R package asd and use it to present some worked-up examples motivated by clinical trials in chronic obstructive pulmonary disease and oncology. The examples both illustrate various features of the R package and provide insights into the operating characteristics of adaptive seamless studies.     

Purpurogallin,a scavenger of polymorphonuclear leukocyte-derived oxyradicals

Purpurogallin (PPG) is a phenolic compound extracted from nutgalls formed on oak trees. It has been used as an additive to edible or nonedible oils or fats, and to hydrocarbon fuels or lubricants to retard their oxidation. We investigated by luminoldependent chemiluminescence (PMNL-CL), the ability of PPG to scavenge oxygen free radicals (OFRs) generated by zymosanactivated polympophonuclear leukocytes (PMNLs). Its OFR-scavenging ability was also investigated by the use of nitro blue tetrazolium (NBT). We also investigated by the dye-exclusion method, if PPG affects the viability of PMNLs. PPG in the concentrations of 0.005–0.4 mM was used in this study. PPG scavenged OFRs produced by zymosan-activated PMNLs in a concentration-dependent manner. Almost complete scavenging was observed at a concentration of 0.2 mM. The NBT test indicated that PPG (0.2 mM) did not completely prevent the activation of PMNLs by zymosan. Viability of PMNLs in the absence or presence of PPG (0.4 mM) were 95.77±0.56% and 96.78±0.60% respectively. The results suggest that PPG scavenges OFRs produced from activated PMNLs in a concentration-dependent manner and that the cell viability is not affected by PPG. PPG is a potent scavenger of OFRs and should be of value in the prevention and treatment of diseases in the pathophysiology of which OFRs are involved. (     

Chemical Composition,Anthelmintic Activity,and Mechanism of Action of Lippia dominguensis Mold. Essential Oil on Haemonchus contortus

Gastrointestinal nematode parasitism is a major burden to small ruminant production globally, compounded by increasing anthelmintic resistance. Previous studies have identified essential oils (EOs) from the Lippia genus with antiprotozoal and anthelmintic effects. Lippia dominguensis Moldenke (Ld), an endemic specie from the Dominican Republic, has similar popular uses, however, is chemically and pharmacologically yet uncharacterized. Here, we investigated the in vitro anthelmintic activity of LdEO and its ultrastructural effects on eggs and adult nematodes of Haemonchus contortus multidrug-resistant isolated. The GC/MS analysis showed linalool (33.85 %), 1,8-cineole (30.88 %), and δ-terpineol (10.61 %) as the main EO constituents. The LdEO showed an IC₅₀=0.523 mg/mL in the egg hatch test, and the motility in the adult worm motility test was 95.8 % at 1 mg/mL. The confocal scanning laser microscopy of eggs indicated permeabilization or disruption of egg cell membranes as the possible mechanism of action of LdEO. The scanning electron microscopy of adult worms showed wrinkling, undulations, and cuticular disruptions. The LdEO displayed significant in vitro anthelmintic activity on eggs and adult worms of H. contortus. Additionally, the LdEO showed low oral toxicity in mice at 2,000 mg/kg. Thus, additional in vivo studies are justified to determine its anthelmintic efficacy in small ruminants.     

食管癌切除术患者运动能力、肌肉力量和生活质量的相关性分析

摘要 目的：探讨食管癌患者术前功能锻炼能力、肌力、焦虑、抑郁和健康相关生活质量（QOL）的特点,并评估食管癌根治术对这些参数的影响。方法：我们对2019年1-12月36例新诊断的可切除食管癌患者进行回顾性分析,这些患者接受了食管切除术并进行了术后康复治疗。术前、术后2周分别进行6 min步行距离（6MWD）、膝伸肌肌力、握力、医院焦虑抑郁量表（HADS）和慢性阻塞性肺疾病（COPD）评定量表（CAT）测试。术前进行肺功能测试,并对MOS 36项目健康问卷（SF-36）的组成部分进行一般健康评定。结果：患者平均年龄66.1±9.2岁。患者以男性为主（75.0%）,有较高的吸烟史（80.6%）,鳞状细胞癌（94.4%）。COPD 15例。临床分期：0-I期11例,II期6例,III期15例,IV期4例。29例行开腹手术。SF-36评分的组成部分与CAT和HADS评分显著相关,COPD患者的身体状况明显差于非COPD患者（P<0.05）。比较术前和术后的数值,发现术后6MWD、握力、等长膝伸肌肌力显著降低,CAT评分显著升高（P<0.05）,HADS评分无明显升高（P>0.05）。在多元回归分析中,术后6MWD的下降与术前SF-36的生理成分总结显著相关。结论：从微创手术和围手术期处理的角度来看,有必要进一步改进围手术期的康复。在手术后两周,食管切除术对健康相关的QOL和身体健康有害,需建立围手术期康复策略,以改善术后结果。     

Anxiety,depression-like behaviors and biochemistry disorders induced by cannabis extract in female mice

Cannabis is an annual herbaceous plant sometimes grown for decoration and used as bird food that looks like flax. The study wanted to determine if a Cannabis extract may have an effect on how anxious and depressed the female mice behaved. forty healthy female mice were divided into four groups. Tap water was administered to the first group (control). Ethanol was administered to second group (positive control). The third and four groups were given 1 and 2 mg/kg cannabis extract respectively. Treatment continued for 14 days. After therapy, the light–dark chamber, forced swimming, tail suspension, plus lamb and open field tests were done to assess anxiety and depressive behavior. The results indicated that the anxiety and depression were increased in treated females significantly compared to control. Biochemical results showed that DA,5-HT, AChE, GSH, GST, CAT and SOD were decreased while TBARS, corticosterone and cortisol were increased. In conclusion, cannabis effects this kind of females’ behavior but the mechanisms are not clear yet. We need more researches on this trend.     

Roche Susceptibility Test (RST) medium,a defined formulation for susceptibility testing: II. Manufacture,stability and use

Methods are described for the laboratory or pilot scale manufacture and use of Roche Susceptibility Test (RST) Medium. Microbiological and quality control analysed show that the product is homogeneous and stable over 12 months at 25°C in an airtight container.     

Responses of an araneophagic assassin bug,Stenolemus bituberus,to spider draglines

Abstract 1. Animals, as they move through their environment, leave traces of their passage that can be informative to others and convey significant advantages to the animal producing them. However, such traces may also reveal presence, location or identity to enemies. 2. We studied an araneophagic (‘spider‐eating’) assassin bug, Stenolemus bituberus (Heteroptera, Reduviidae), testing whether it associated with areas containing chemotactile traces (e.g. draglines, excreta) left behind by nine sympatric spider species. Stenolemus bituberus were presented with a choice between a substrate containing draglines and a clean substrate. Each hour, for a duration of 12 h, we recorded which substrate was occupied. 3. Stenolemus bituberus tended to associate especially with draglines left by spiders from the genus Achaearanea, their most common prey in nature. 4. These results suggest that S. bituberus exploits draglines from these spiders as cues for indicating prey presence. We also found an increasing tendency to associate with draglines from some spider species through the day, which may be related to circadian patterns or slower response times of some individuals.